Adjacently linked polyether residues comprise the structure of several classes of natural products which have a wide range of important biological activities. Among these compounds are the ionophore antibiotics, (anticoccidial, cardiovascular, anti-HIV) and the acetogenins (antitumors). The long term goal of this project is the development of a novel methodology for the preparation of the highly substituted polyether that comprise the structure of these compounds. The synthetic plan is based on a new method for the formation of 2,5- disubstituted tetrahydrofurans (THF's). Via this procedure, a monosaccharide alkene precursor on treatment with halonium ion under aqueous conditions, is directly converted to a highly substituted halo- THF-aldehyde. The reaction is based on neighboring group participation by the ring oxygen of the monosaccharide. The short term goal will be optimization of the stereoselectivity of this reaction. A key aspect of this study requires the use of the aglucone substituent as a stereocontrolling element. In order to formulate a set of rules for predicting steroselectivity, the reactions of monosaccharide alkenes in which the size, electronic properties and configuration of the aglycone are varied, will be performed. Simultaneously the activating or deactivating effects of aglycone structure on the rate of the reaction will be noted. The rules for predicting steroselectivity and reactivity will be subsequently incorporated into a novel plan for the preparation of adjacently linked polyether, containing up to four units, from bis- saccharide alkene precursors. Due to its carbohydrate origin, this methodology will be especially suitable for preparation of highly hydroxylate polyether derivatives. In addition, the convergent nature of the plan and the availability of naturally occurring sugars of diverse substitution pattern facilitates a high degree of structural 'fine tuning', making the method attractive for drug analog production.